Table 8 Management of cytopenias
TKI | Setting and starting dose | Hematopoietic toxicity | Dose adjustments for neutropenia and thrombocytopenia |
|---|---|---|---|
Imatinib | CP, 400 mg daily | ANC <1.0 × 109/l and/or platelets <50 × 109/l | (1) Stop imatinib until ANC >1.5 × 109/l and platelets>75 × 109/l>resume starting dose (2) Recurrence: repeat step 1 and resume at the reduced dose of 300 mg daily |
AP and BP, 600 mg daily | ANC <0.5 × 109/l and/or platelets <10 × 109/l | (1) Check if neutropenia is related to leukaemia (marrow aspiration or biopsy) (2) If UNRELATED, reduce imatinib to 400 mg daily (3) If cytopenia persists >2 weeks, reduce to 300 mg daily If cytopenia persists for >4 weeks and is still unrelated to leukaemia, stop imatinib until ANC⩾1 × 109/l and platelets ⩾20 × 109/l and resume at 300 mg daily | |
Nilotinib | CP, frontline, 300 mg twice daily CP, second line, or AP, 400 mg twice daily | ANC <1.0 × 109/l and/or platelets <50 × 109/l | (1) Stop nilotinib until ANC >1.0 × 109/l and platelets>50 × 109/l>resume starting dose (2) If blood counts remain low for >2 weeks, resume at 400 mg daily |
Dasatinib | CP, 100 mg daily | ANC <0.5 × 109/l and/or platelets <50 × 109/l | (1) Stop dasatinib until ANC >1.0 × 109/l and platelets>50 × 109/l>resume the original starting dose (2) If platelets <25 × 109/l and/or recurrence of ANC <0.5 × 109/l, repeat step 1 and resume dasatinib at a reduced dose of 80 mg once daily for the second episode. For third episode, further reduce to 50 mg daily (newly diagnosed patients) or discontinue dasatinib (for patients resistant or intolerant to prior therapy including imatinib) |
Dasatinib | AP, BP and Ph+ ALL, 140 mg daily | ANC <0.5 × 109/l and/or platelets <10 × 109/l | (1) Check if neutropenia is related to leukaemia (marrow aspiration or biopsy) (2) If UNRELATED to leukaemia, stop dasatinib until ANC ⩾1.0 × 109/l and platelets ⩾20 × 109/l and resume the original dose (3) If recurrence of cytopenia, repeat step 1 and resume dasatinib at a reduced dose of 100 mg once daily (second episode) or 80 mg once daily (third episode) (4) If cytopenia is related to leukaemia, consider dose escalation to 180 mg once daily |
Bosutinib | CP, AP, BP CML, 500 mg daily | ANC <1.0 × 109/l and/or platelets <50 × 109/l | (1) Withhold bosutinib until ANC ⩾1.0 × 109/l and platelets ⩾50 × 109/l (2) Resume treatment with bosutinib at the same dose if recovery occurs within 2 weeks. If blood counts remain low for >2 weeks, reduce dose by 100 mg and resume treatment (3) If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment Doses <300 mg/day have not been evaluated |
Ponatinib | CML, CP, AP and BP or Ph+ ALL, 45 mg daily | ANC <1.0 × 109/l and/or platelets <50 × 109/l | (1) First episode: stop ponatinib until ANC >1.5 × 109/l and platelets >75 × 109/l and resume at 45 mg daily (2) Second episode: stop ponatinib until ANC >1.5 × 109/l and platelets >75 × 109/l and resume at 30 mg daily (3) Third episode: stop ponatinib until ANC >1.5 × 109/l and platelets >75 × 109/l and resume at 15 mg daily |
